Covalent Inhibition Achieves Superior Potency Against Drug-Resistant HCV Mutants
BOSTON and WALTHAM, MA – Avila Therapeutics™, Inc., a biotechnology company developing novel targeted covalent drugs, presented results today of preclinical studies that demonstrate its orally-available targeted covalent drug candidate, AVL-192, achieves superior potency against drug-resistant mutations of the Hepatitis C Virus (HCV). These new data were presented today at the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) international meeting in Boston, Massachusetts.
HCV protease (also known as NS3) is a promising target of intervention for the treatment of hepatitis C infection. However, medicines currently in late stages of clinical development are vulnerable to drugresistant mutations. AVL-192 is a novel, orally available compound that can rapidly and completely silence the HCV protease through highly selective, irreversible covalent bonding to the target protein. Preclinical data have demonstrated that AVL-192 achieves very high potency and selectivity for NS3 and also potently and effectively inhibits the drug-resistant mutations observed clinically.
Avila’s covalent approach to silencing the NS3 protein has resulted in a product candidate with a potential best-in-class profile due to the ability to retain potency against clinically-arising resistance
mutations, and potential breadth of activity across HCV genotypes with anticipated once-per-day dosing.
In a poster presentation at the meeting, entitled, “Second Generation of Covalent Irreversible Inhibitors Have Superior Potency Across Genotypes and Drug Resistant Mutants,” data were presented from preclinical studies that evaluated the efficacy of AVL-192 in biochemical and cell culture studies.
Highlights of the data demonstrate:
• AVL-192 has a time-dependent mode of action that delivers potent and rapid inhibition of WT NS3/4A and retains high potency against drug-resistant mutant NS3/4A proteases;
• AVL-192 is able to inhibit the protease long after the compound is removed, offering the benefit of less frequent dosing;
• AVL-192 as monotherapy can be curative in the replicon clearance assay;
• AVL-192 is highly selective and spares host proteases; and
• AVL-192 has high plasma exposure following oral administration in rats and dogs. “These new data reinforce our belief that our targeted covalent drug candidate AVL-192 has the potential to be a best-in-class, pan-genotype HCV therapeutic due to its unique mechanism of action,” said Juswinder Singh, Ph.D., Avila’s Founder and Chief Scientific Officer.
About Avila Therapeutics™, Inc.
Avila focuses on design and development of targeted covalent drugs to achieve best-in-class outcomes that cannot be achieved through traditional chemistries. This approach is called “protein silencing”. The company’s product pipeline has been built using its proprietary Avilomics™ platform and is currently focused on viral infection, cancer and autoimmune disease. Avila is funded by leading venture capital firms: Abingworth, Advent Venture Partners, Atlas Venture, Novartis Option Fund, and Polaris Venture Partners.